{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:27:15Z","timestamp":1787840835826,"version":"build-2784847793"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003803","name":"The University of Hong Kong","doi-asserted-by":"crossref","award":["201611159217"],"award-info":[{"award-number":["201611159217"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL\/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), and tumor necrosis factor-\u03b1 (TNF-\u03b1). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor (VEGF) in the spinal cord.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings support that glutamate excitotoxicity and neuroinflammation play important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-020-01913-2","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T06:05:33Z","timestamp":1597125933000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders"],"prefix":"10.1186","volume":"17","author":[{"given":"Leung-Wah","family":"Yick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ho","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar Ka-Fai","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Shing-Cheong","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4665-2576","authenticated-orcid":false,"given":"Koon-Ho","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"1913_CR1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/nyas.12794","volume":"1366","author":"SJ Pittock","year":"2016","unstructured":"Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: A decade later. Ann N Y Acad Sci. 2016;1366:20\u201339.","journal-title":"Ann N Y Acad Sci."},{"key":"1913_CR2","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","volume":"364","author":"VA Lennon","year":"2004","unstructured":"Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet. 2004;364:2106\u201312.","journal-title":"Lancet."},{"key":"1913_CR3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1084\/jem.20050304","volume":"202","author":"VA Lennon","year":"2005","unstructured":"Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202:473\u20137.","journal-title":"J Exp Med."},{"key":"1913_CR4","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrneurol.2014.141","volume":"10","author":"MC Papadopoulos","year":"2014","unstructured":"Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10:493\u2013506.","journal-title":"Nat Rev Neurol."},{"key":"1913_CR5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/bpa.12099","volume":"24","author":"CF Lucchinetti","year":"2014","unstructured":"Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: Lessons learned from neuromyelitis optica. Brain Pathol. 2014;24:83\u201397.","journal-title":"Brain Pathol."},{"key":"1913_CR6","doi-asserted-by":"crossref","unstructured":"Popescu BF, Lucchinetti CF. Immunopathology: Autoimmune glial diseases and differentiation from multiple sclerosis. 1st ed. Handb. Clin. Neurol. Elsevier B.V. 2016.","DOI":"10.1016\/B978-0-12-800763-1.00009-9"},{"key":"1913_CR7","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00401-013-1116-7","volume":"125","author":"T Misu","year":"2013","unstructured":"Misu T, H\u00f6ftberger R, Fujihara K, Wimmer I, Takai Y, Nishiyama S, Nakashima I, Konno H, Bradl M, Garzuly F, Itoyama Y, Aoki M, Lassmann H. Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica. Acta Neuropathol. 2013;125:815\u201327.","journal-title":"Acta Neuropathol."},{"key":"1913_CR8","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1212\/01.WNL.0000289761.64862.ce","volume":"69","author":"SR Hinson","year":"2007","unstructured":"Hinson SR, Pittock SJ, Lucchinetti CF. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007;69:2221\u201331.","journal-title":"Neurology."},{"key":"1913_CR9","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1084\/jem.20081241","volume":"205","author":"SR Hinson","year":"2008","unstructured":"Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, Howe CL, Pittock SJ, Lennon VA. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med. 2008;205:2473\u201381.","journal-title":"J Exp Med."},{"key":"1913_CR10","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1073\/pnas.1701960114","volume":"114","author":"SR Hinson","year":"2017","unstructured":"Hinson SR, CliftI C, Luo N, Kryzer TJ, Lennon VA. Autoantibody-induced internalization of CNS AQP4 water channel and EAAT2 glutamate transporter requires astrocytic Fc receptor. Proc Natl Acad Sci. 2017;114:5491\u20136.","journal-title":"Proc Natl Acad Sci."},{"key":"1913_CR11","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/glia.22635","volume":"62","author":"CL Howe","year":"2014","unstructured":"Howe CL, Kaptzan T, Maga\u00f1a SM, Ayers-Ringler JR, Lafrance-Corey RG, Lucchinetti CF. Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures. Glia. 2014;62:692\u2013708.","journal-title":"Glia."},{"key":"1913_CR12","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00401-013-1172-z","volume":"126","author":"J Ratelade","year":"2013","unstructured":"Ratelade J, Asavapanumas N, Ritchie AM, Wemlinger S, Bennett JL, Verkman AS. Involvement of antibody-dependent cell-mediated cytotoxicity in inflammatory demyelination in a mouse model of neuromyelitis optica. Acta Neuropathol. 2013;126:699\u2013709.","journal-title":"Acta Neuropathol."},{"key":"1913_CR13","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3389\/fimmu.2018.01438","volume":"9","author":"LW Yick","year":"2018","unstructured":"Yick LW, Ma OKF, Ng RCL, Kwan JSC, Chan KH. Aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder patients induce complement-independent immunopathologies in mice. Front Immunol. 2018;9:1438.","journal-title":"Front Immunol."},{"key":"1913_CR14","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S1474-4422(09)70146-2","volume":"8","author":"D Aarsland","year":"2009","unstructured":"Aarsland D, Ballard C, Walker Z, Bostrom F, Alves G, Kossakowski K, Leroi I, Pozo-Rodriguez F, Minthon L, Londos E. Memantine in patients with Parkinson\u2019s disease dementia or dementia with Lewy bodies: A double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8:613\u20138.","journal-title":"Lancet Neurol."},{"key":"1913_CR15","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1056\/NEJMoa013128","volume":"348","author":"B Reisberg","year":"2003","unstructured":"Reisberg B, Doody R, St\u00f6ffler A, Schmitt F, Ferris S, M\u00f6bius HJ. Memantine in moderate-to-severe Alzheimer\u2019s disease. N Engl J Med. 2003;348:1333\u201341.","journal-title":"N Engl J Med."},{"key":"1913_CR16","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1097\/NEN.0000000000000073","volume":"73","author":"KW Suhs","year":"2014","unstructured":"Suhs KW, Fairless R, Williams SK, Heine K, Cavalie A, Diem R. N-methyl-D-aspartate receptor blockade is neuroprotective in experimental autoimmune optic neuritis. J Neuropathol Exp Neurol. 2014;73:507\u201318.","journal-title":"J Neuropathol Exp Neurol."},{"key":"1913_CR17","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/glia.22781","volume":"63","author":"WK Ju","year":"2015","unstructured":"Ju WK, Kim KY, Noh YH, Hoshijima M, Lukas TJ, Ellisman MH, Weinreb RN, Perkins GA. Increased mitochondrial fission and volume density by blocking glutamate excitotoxicity protect glaucomatous optic nerve head astrocytes. Glia. 2015;63:736\u201353.","journal-title":"Glia."},{"key":"1913_CR18","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1007\/s12035-014-8767-9","volume":"51","author":"CY Huang","year":"2015","unstructured":"Huang CY, Wang LC, Wang HK, Pan CH, Cheng YY, Shan YS, Chio CC, Tsai KJ. Memantine alleviates brain injury and neurobehavioral deficits after experimental subarachnoid hemorrhage. Mol Neurobiol. 2015;51:1038\u201352.","journal-title":"Mol Neurobiol."},{"key":"1913_CR19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1742-2094-7-50","volume":"7","author":"KH Chan","year":"2010","unstructured":"Chan KH, Kwan JSC, Ho PWL, Ho JWM, Chu ACY, Ramsden DB. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays. J Neuroinflammation. 2010;7:50.","journal-title":"J Neuroinflammation"},{"key":"1913_CR20","first-page":"2376","volume":"49","author":"TN Luong","year":"2011","unstructured":"Luong TN, Carlisle HJ, Southwell A, Patterson PH. Assessment of motor balance and coordination in mice using the balance beam. J Vis Exp. 2011;49:2376.","journal-title":"J Vis Exp."},{"key":"1913_CR21","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.molimm.2014.06.003","volume":"62","author":"J Ratelade","year":"2014","unstructured":"Ratelade J, Verkman AS. Inhibitor(s) of the classical complement pathway in mouse serum limit the utility of mice as experimental models of neuromyelitis optica. Mol Immunol. 2014;62:104\u201313.","journal-title":"Mol Immunol."},{"key":"1913_CR22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2012.08.008","volume":"254","author":"S Rai","year":"2013","unstructured":"Rai S, Kamat PK, Nath C, Shukla R. A study on neuroinflammation and NMDA receptor function in STZ (ICV) induced memory impaired rats. J Neuroimmunol. 2013;254:1\u20139.","journal-title":"J Neuroimmunol."},{"key":"1913_CR23","doi-asserted-by":"crossref","first-page":"495","DOI":"10.5607\/en.2019.28.4.495","volume":"28","author":"CH Jang","year":"2019","unstructured":"Jang CH, Lee S, Park IY, Song A, Moon C, Cho GW. Memantine attenuates salicylate-induced tinnitus possibly by reducing NR2B expression in auditory cortex of rat. Exp Neurobiol. 2019;28:495\u2013503.","journal-title":"Exp Neurobiol."},{"key":"1913_CR24","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1177\/0271678X16648971","volume":"37","author":"YC Wang","year":"2017","unstructured":"Wang YC, Sanchez-Mendoza EH, Doeppner TR, Hermann DM. Post-Acute delivery of memantine promotes post-ischemic neurological recovery, peri-infarct tissue remodeling, and contralesional brain plasticity. J Cereb Blood Flow Metab. 2017;37:980\u201393.","journal-title":"J Cereb Blood Flow Metab."},{"key":"1913_CR25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","volume":"35","author":"M Colonna","year":"2017","unstructured":"Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol. 2017;35:441\u201368.","journal-title":"Annu Rev Immunol."},{"key":"1913_CR26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/157015908783769671","volume":"6","author":"C Parsons","year":"2008","unstructured":"Parsons C, Rammes G, Danysz W. Pharmacodynamics of memantine: an update. Curr Neuropharmacol. 2008;6:55\u201378.","journal-title":"Curr Neuropharmacol."},{"key":"1913_CR27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1602\/neurorx.1.1.101","volume":"1","author":"SA Lipton","year":"2004","unstructured":"Lipton SA. Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx. 2004;1:101\u201310.","journal-title":"NeuroRx."},{"key":"1913_CR28","doi-asserted-by":"crossref","unstructured":"Hinson SR, Lennon VA, Pittock SJ. Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders. Handb Clin Neurol 1st ed. Elsevier B.V. 2016;377\u2013403.","DOI":"10.1016\/B978-0-444-63432-0.00021-9"},{"key":"1913_CR29","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s12640-018-9958-3","volume":"35","author":"K Skowro\u0144ska","year":"2018","unstructured":"Skowro\u0144ska K, Obara-Michlewska M, Czarnecka A, D\u0105browska K, Zieli\u0144ska M, Albrecht J. Persistent overexposure to N-Methyl-d-Aspartate (NMDA) calcium-dependently downregulates glutamine synthetase, aquaporin 4, and Kir4.1 channel in mouse cortical astrocytes. Neurotox Res. 2018;35:271\u201380.","journal-title":"Neurotox Res."},{"key":"1913_CR30","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3390\/cells8020184","volume":"8","author":"S Mahmoud","year":"2019","unstructured":"Mahmoud S, Gharagozloo M, Simard C, Gris D. Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release. Cells. 2019;8:184.","journal-title":"Cells"},{"key":"1913_CR31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.pneurobio.2016.03.009","volume":"144","author":"AR Filous","year":"2016","unstructured":"Filous AR, Silver J. Targeting astrocytes in CNS injury and disease: A translational research approach. Prog Neurobiol. 2016;144:173\u201387.","journal-title":"Prog Neurobiol."},{"key":"1913_CR32","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1093\/brain\/awq177","volume":"133","author":"R Marignier","year":"2010","unstructured":"Marignier R, Nicolle A, Watrin C, Touret M, Cavagna S, Varrin-Doyer M, Cavillon G, Rogemond V, Confavreux C, Honnorat J, Giraudon P. Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain. 2010;133:2578\u201391.","journal-title":"Brain."},{"key":"1913_CR33","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/0269881118754680","volume":"32","author":"J Olloquequi","year":"2018","unstructured":"Olloquequi J, Cornejo-C\u00f3rdova E, Verdaguer E, Soriano FX, Binvignat O, Auladell C, Camins A. Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications. J Psychopharmacol. 2018;32:265\u201375.","journal-title":"J Psychopharmacol."},{"key":"1913_CR34","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12974-016-0577-8","volume":"13","author":"R Marignier","year":"2016","unstructured":"Marignier R, Ruiz A, Cavagna S, Nicole A, Watrin C, Touret M, Parrot S, Malleret G, Peyron C, Benetollo C, Auvergnon N, Vukusic S, Giraudon P. Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid. J Neuroinflammation. 2016;13:111.","journal-title":"J Neuroinflammation."},{"key":"1913_CR35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/s12974-016-0746-9","volume":"13","author":"CM Felix","year":"2016","unstructured":"Felix CM, Levin MH, Verkman AS. Complement-independent retinal pathology produced by intravitreal injection of neuromyelitis optica immunoglobulin G. J Neuroinflammation. 2016;13:275.","journal-title":"J Neuroinflammation."},{"key":"1913_CR36","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jneuroim.2013.05.006","volume":"261","author":"G Sulkowski","year":"2013","unstructured":"Sulkowski G, Dabrowska-Bouta B, Chalimoniuk M, Struzy\u0144ska L. Effects of antagonists of glutamate receptors on pro-inflammatory cytokines in the brain cortex of rats subjected to experimental autoimmune encephalomyelitis. J Neuroimmunol. 2013;261:67\u201376.","journal-title":"J Neuroimmunol."},{"key":"1913_CR37","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.neulet.2016.07.016","volume":"629","author":"KW S\u00fchs","year":"2016","unstructured":"S\u00fchs KW, Gudi V, Eckermann N, Fairless R, Pul R, Skripuletz T, Stangel M. Cytokine regulation by modulation of the NMDA receptor on astrocytes. Neurosci Lett. 2016;629:227\u201333.","journal-title":"Neurosci Lett."},{"key":"1913_CR38","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1038\/npp.2009.64","volume":"34","author":"HM Wu","year":"2009","unstructured":"Wu HM, Tzeng NS, Qian L, Wei SJ, Hu X, Chen SH, Rawls SM, Flood P, Hong JS, Lu RB. Novel neuroprotective mechanisms of memantine: Increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation. Neuropsychopharmacology. 2009;34:2344\u201357.","journal-title":"Neuropsychopharmacology."},{"key":"1913_CR39","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3109\/00207454.2011.598981","volume":"121","author":"S Singh","year":"2011","unstructured":"Singh S, Swarnkar S, Goswami P, Nath C. Astrocytes and microglia: Responses to neuropathological conditions. Int J Neurosci. 2011;121:589\u201397.","journal-title":"Int J Neurosci."},{"key":"1913_CR40","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/mcne.2001.1027","volume":"18","author":"M Marvanov\u00e1","year":"2001","unstructured":"Marvanov\u00e1 M, Lakso M, Pirhonen J, Nawa H, Wong G, Castr\u00e9n E. The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain. Mol Cell Neurosci. 2001;18:247\u201358.","journal-title":"Mol Cell Neurosci."},{"key":"1913_CR41","doi-asserted-by":"crossref","first-page":"6730","DOI":"10.1007\/s12035-015-9576-5","volume":"53","author":"N Rajasekar","year":"2016","unstructured":"Rajasekar N, Nath C, Hanif K, Shukla R. Inhibitory effect of memantine on streptozotocin-induced insulin receptor dysfunction, neuroinflammation, amyloidogenesis, and neurotrophic factor decline in astrocytes. Mol Neurobiol. 2016;53:6730\u201344.","journal-title":"Mol Neurobiol."},{"key":"1913_CR42","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1002\/glia.22411","volume":"60","author":"Y Koyama","year":"2012","unstructured":"Koyama Y, Maebara Y, Hayashi M, Nagae R, Tokuyama S, Michinaga S. Endothelins reciprocally regulate VEGF-A and angiopoietin-1 production in cultured rat astrocytes: Implications on astrocytic proliferation. Glia. 2012;60:1954\u201363.","journal-title":"Glia."},{"issue":"1","key":"1913_CR43","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12974-017-0882-x","volume":"14","author":"SS Dusaban","year":"2017","unstructured":"Dusaban SS, Chun J, Rosen H, Purcell NH, Brown JH. Sphingosine 1-phosphate receptor 3 and RhoA signaling mediate inflammatory gene expression in astrocytes. J Neuroinflammation. 2017;14(1):111.","journal-title":"J Neuroinflammation."},{"key":"1913_CR44","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1161\/STROKEAHA.113.004476","volume":"45","author":"HE L\u00f3pez-Vald\u00e9s","year":"2014","unstructured":"L\u00f3pez-Vald\u00e9s HE, Clarkson AN, Ao Y, Charles AC, Carmichael ST, Sofroniew MV, Brennan KC. Memantine enhances recovery from stroke. Stroke. 2014;45:2093\u2013100.","journal-title":"Stroke."},{"key":"1913_CR45","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12031-017-0974-1","volume":"63","author":"N Zhang","year":"2017","unstructured":"Zhang N, Song C, Zhao B, Xing M, Luo L, Gordon ML, Cheng Y. Neovascularization and synaptic function regulation with memantine and rosuvastatin in a rat model of chronic cerebral hypoperfusion. J Mol Neurosci. 2017;63:223\u201332.","journal-title":"J Mol Neurosci."},{"key":"1913_CR46","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.neuropharm.2007.07.013","volume":"53","author":"CG Parsons","year":"2007","unstructured":"Parsons CG, St\u00f6ffler A, Danysz W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse. Neuropharmacology. 2007;53:699\u2013723.","journal-title":"Neuropharmacology."}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01913-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01913-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01913-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T08:57:47Z","timestamp":1667725067000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01913-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,11]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1913"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01913-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-27104\/v1","asserted-by":"object"}]},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,11]]},"assertion":[{"value":"3 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Informed consent for using serum\/plasma samples in the study was obtained from all study subjects. The experiments on C57BL\/6 mice were approved by the Committee on the Use of Live Animals in Teaching and Research of The University of Hong Kong.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors read and approved the final manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"236"}}